Pharmacological prevention of cardiovascular aging--targeting the Maillard reaction

Abstract

The development of myocardial and large vessel stiffness with aging underlies the development of diastolic heart failure and isolated systolic hypertension. Nonenzymatic reaction between glucose and proteins (Maillard reaction) leading to collagen crosslinking in the myocardium and arterial wall has been implicated in age-related increase in cardiovascular stiffness. In the present issue, Chang et al. show that aminoguanidine, an inhibitor of protein crosslinking, retards age-related decline in the elastic properties of the left ventricle and arteries. The significance of these findings is discussed in this commentary.

Figure 1

Schematic description of the formation of collagen crosslinks and strategies for blocking the formation of AGEs and AGE crosslinks. Glucose attaches to an amino group of a protein such as collagen to form a Schiff base, which subsequently transforms itself into an Amadori product. The latter can pass through several incompletely understood steps (broken arrows) to become an AGE. AGEs can react with free amino groups on an adjacent protein to form crosslinks. Crosslinking can lead to a decrease in large vessels and myocardial compliance, resulting in heart failure with preserved systolic function and/or systolic hypertension (see text for details).